新生儿红细胞葡萄糖6磷酸脱氢酶缺乏与高胆红素血症临床分析

新生儿高胆红素血症由多种病因所致，红细胞葡萄糖6磷酸脱氢酶（G6PD）缺乏症是新生儿发生高胆红素血症重要原因之一，本研究探讨新生儿G6PD缺乏合并高胆红素血症的发病特点及G6PD活性降低与性别的关系。     

新生儿红细胞葡萄糖6磷酸脱氢酶缺乏与高胆红素血症临床分析

新生儿高胆红素血症由多种病因所致,红细胞葡萄糖6磷酸脱氢酶(G6PD)缺乏症是新生儿发生高胆红素血症重要原因之一,本研究探讨新生儿G6PD缺乏合并高胆红素血症的发病特点及G6PD活性降低与性别的关系。资料与方法一、对象和诊断标准足月高胆红素血症诊断标准:血清总胆红素24h>102·6μmol/L,48h>154μmol/L,3d以上>220·6μmol/L,以间接胆红素为主;G6PD缺乏的诊断标准:G6PD活性<10U/gHb[1]。对伴有巨细胞病毒、单纯疱疹病毒、风疹病毒、弓形虫感染、地中海贫血、ABO溶血、红细胞增多症的患儿予以剔除。2003年1月至2006年1月收入我院…     

G-6-PD缺乏新生儿高胆红素血症发病机制的研究进展

在我国南方 ,葡萄糖 6 磷酸脱氢酶 (G 6 PD)缺乏是新生儿高胆红素血症的主要病因。新生儿G 6 PD缺乏的最大危害为可引起高胆红素血症与核黄疸。G 6 PD缺乏所致新生儿高胆红素血症的发病机制是多因素共同作用的结果 ,既往强调溶血是其发病的主因 ,目前认为胆红素结合能力不足也参与发病。UGT1A1基因突变导致胆红素结合障碍是 2 1世纪的研究热点。不少学者提出UGT1A1基因突变与G 6 PD缺乏二者对高胆红素血症起协同作用。     

男性新生儿红细胞葡萄糖-6-磷酸脱氢酶活性中度缺乏的探讨

目的探讨男性新生儿红细胞葡萄糖6磷酸脱氢酶(G6PD)活性中度缺乏的原因。方法根据遗传规律,把G6PD活性分为正常、中度缺乏和显著缺乏,并对我院2000年至2005年10月出生的10733名新生儿的资料与各地检测G6PD活性报道的资料进行比较、分析和研究。结果男性新生儿G6PD活性中度缺乏发生率约为1.5%～2.5%(约占男性新生儿G6PD活性总缺乏率的15%～25%)。结论本研究发现男性新生儿G6PD活性中度缺乏是客观存在的并和孟德尔遗传定律矛盾,它与G6PD变异型的酶活性表现、统计学方法、糖尿病和溶血等多种因素等有关。     

男性新生儿红细胞葡萄糖-6-磷酸脱氢酶活性中度缺乏的探讨

目的探讨男性新生儿红细胞葡萄糖-6-磷酸脱氢酶（G6PD）活性中度缺乏的原因。方法根据遗传规律，把G6PD活性分为正常、中度缺乏和显著缺乏，并对我院2000年至2005年10月出生的10733名新生儿的资料与各地检测G6PD活性报道的资料进行比较、分析和研究。结果男性新生儿G6PD活性中度缺乏发生率约为1．5％～2．5％（约占男性新生儿G6PD活性总缺乏率的15％～25％）。结论本研究发现男性新生儿G6PD活性中度缺乏是客观存在的并和孟德尔遗传定律矛盾，它与G6PD变异型的酶活性表现、统计学方法、糖尿病和溶血等多种因素等有关。     

高胆红素血症新生儿G6PD缺陷合并HCMV感染的分析

目的　新生儿葡萄糖 6 磷酸脱氢酶 (G6PD)缺乏常在一些诱发因素如感染等情况下导致溶血 ,引起高胆红素血症 ,巨细胞病毒感染是先天性感染的主要病因之一。该文对高胆红素血症的新生儿G6PD缺陷与巨细胞病毒 (HCMV)感染的关系及临床特点进行探讨。方法　对 31 6例临床确诊为高胆红素血症的新生儿进行G6PD/6PGD比值、PCRHCMV及红细胞、血红蛋白、胆红素等各项指标的测定 ,并进行比较。结果　G6PD缺陷和HCMV感染之间存在着相关性 (P <0 .0 5 ) ,且两者合并存在的患儿比单纯G6PD缺陷或单纯HCMV感染时的红细胞、血红蛋白减低 ,而且总胆红素 (TB)、间接胆红素 (IB)显著升高 (P <0 .0 5 )。结论　HCMV感染易诱发G6PD缺陷的新生儿发生高胆红素血症 ,并使黄疸加重。     

抗体释放试验与新生儿高胆红素血症发生率关系探讨

目的 探讨抗体释放试验不同的检验结果与新生儿高胆红素血症发生率的关系.方法 按检验操作规程,对1 013例母/子血型O/A(B)组合的新生儿脐血进行溶血性疾病血型血清学检验.按检验结果分组调查其出生7 d内高胆红素血症的发生率.结果 (1)抗体释放试验阳性患儿高胆红素血症发生率显著高于对照组的新生儿(P＜0.01).(2)在抗体释放试验阳性结果中,红细胞凝集程度不同的三组患儿高胆红素血症发生率差异有显著性(P＜0.01).(3)抗体释放试验阳性患儿是否存在IgG抗-A+B的两组患儿高胆红素血症发生率差异无显著性(P＞0.05);是否存在游离抗体的两组患儿高胆红素血症发生率差异有显著性(P＜0.01).结论 抗体释放试验不同的检验结果对判断新生儿能否发生高胆红素血症有一定的临床意义.     

单中心新生儿高胆红素血症死亡病例分析

目的探讨新生儿严重高胆红素血症死亡病例的病因、临床特点、基因突变情况。方法选取2013年1月至2022年12月复旦大学附属儿科医院新生儿病区收治的结局为死亡的严重高胆红素血症患儿作为研究对象, 对其临床特点、病因、实验室检查、基因检测结果进行回顾性分析。结果共纳入4例结局为死亡的严重高胆红素血症患儿, 均为男性, 其中足月儿2例, 早产儿2例, 胎龄中位数(范围)为37.6(35+6～39+1)周, 出生体重中位数(范围)3 055(2 600, 3 440)g, 入院日龄中位数(范围)为6.5(4.0, 8.0)d, 死亡日龄中位数(范围)为7.5(6.0, 19.0)d, 入院生化总胆红素中位数(范围)为591.7(379.0, 656.2)μmol/L。所有病例入院时均存在神经系统症状和(或)体征, 3例患儿存在神经系统外受累表现。全部病例均存在葡萄糖-6-磷酸脱氢酶(G6PD)缺乏症, 其中2例还同时存在血培养阳性的新生儿败血症, 1例为可疑感染。3例接受了基因检查, 证实存在G6PD基因变异, 其中1例合并有UGT1A1基因变异。结论新生儿高胆红素血症中, 需重视G6PD缺乏...     

ABO血型系统新生儿溶血病早期诊断探讨

目的 通过对脐血做免疫血清学检验,探讨新生儿溶血病的早期诊断方法.方法 按检验操作规程,对916例母/子血型O/A(B)组合的新生儿脐血进行免疫血清学检验,对红细胞被IgG抗-A(B)致敏的患儿,在出生7 d内分组调查其高胆红素血症的发生率及发病时间.结果 (1)脐血抗体释放试验阳性患儿与对照组比较,新生儿高胆红素血症发生率差异有显著性(P<0.01).不同分娩胎次患儿发生高胆红素血症的差异无显著性(P>0.05).(2)抗体释放试验阳性者血液中存在与不存在游离抗体的两组患儿,高胆红素血症发生率比较差异有显著性(P<0.01).(3)抗体释放试验阳性患儿发生高胆红素血症的高峰时间在出生后的1～3 d.结论 对脐血进行免疫血清学检验,可早期诊断新生儿溶血病,血液中存在的游离抗体有助于判断疾病的发展趋势.     

遗传因素在广西新生儿高胆红素血症中的作用

目的探讨UGT1A1 G71R突变、OATP2A388G突变和G-6-PD缺乏对在广西新生儿高胆红素血症发病的作用。方法用四氮唑蓝定量法（NBT法）测定G-6-PD酶活性。聚合酶链反应-等位基因特异性寡核苷酸探针点杂交（PCR-ASO）法确定G71R基因型。限制性片段长度多态性分析（RFLP）检测A388G基因型。测定109例新生儿脐血的G-6-PD活性及G71R基因型,其中101例同时检测了A388G基因型。据G-6-PD活性及G71R或A388G基因型分组,分析UGT1A1G71R突变、OATP2A388G突变和G-6-PD缺乏与足月新生儿高胆红素血症之间关系。结果G71R等位基因频率在G-6-PD缺乏组为22．03％,在G-6-PD正常组为28．00％。G-6-PD缺乏共存有G71R突变纯合子或杂合子的新生儿高胆红素血症发生率（95．50％）高于G-6-PD正常且G71R为野生型的新生儿（53．90％）,x^2=10．45,P=0．0012,前者发生高胆红素血症的机会比（95％可信区间）[OR（95％CI）]为18．00（2．12,152．9）。A388G等位基因频率在G-6-PD缺乏组为20．O％,在G-6-PD正常组为18．5％。G-6-PD缺乏共存有A388G突变新生儿的高胆红素血症发生率（90．0％）高于G-6-PD正常且A388G为野生型的新生）L（44．80％）,X2=10．39,P=0．0013,前者发生高胆红素血症的伽（95％CT）为11．08（2．15,56．48）。结论G71R突变与G-6-PD缺乏共存或A388G突变与G-6-PD缺乏共存对广西足月新生儿高胆红素血症的发生有协同作用。     

Hyperbilirubinemia in healthy neonates with glucose-6-phosphate dehydrogenase deficiency

A cohort study was carried out to assess the association between glucose-6-phosphate dehydrogenase (G6PD) deficiency, diagnosed by quantitative enzyme assay, and neonatal hyperbilirubinemia, defined as serum total bilirubin >/=15 mg/dl, in the well-baby nursery of Chang Gung Children's Hospital. Among 42,110 inborn infants, 757 male (3.54%) and 326 female (1.57%) newborns were G6PD-deficient. Compared to the occurrence of hyperbilirubinemia in G6PD-normal newborns (1.41% in male, 1.44% in female) in the well-baby nursery, a significantly higher incidence was observed in both G6PD-deficient male (11.36%) and female (7.06%) newborns. Further analyses demonstrated that the enzyme activity of G6PD in G6PD-deficient male newborns with hyperbilirubinemia (1.56+/-1.37 U/g Hb) were significantly lower than the subjects without hyperbilirubinemia (2.01+/-1.7 U/g Hb). No significant difference was observed in G6PD-deficient female newborns with hyperbilirubinemia (6.91+/-2.76 U/g Hb) compared to those without hyperbilirubinemia (7.81+/-2.84 U/g Hb). These data suggest that the G6PD-deficient neonates are at increased risk for hyperbilirubinemia even in the nursery free from agents that can potentially cause hemolysis to G6PD-deficient red cells. The lower G6PD enzyme activity was associated with the neonatal hyperbilirubinemia in G6PD-deficient male neonates.     

GLUCOSE-6-PHOSPHATE DEHYDROGENASE AND RED CELL PYRUVATE KINASE DEFICIENCY IN NEONATAL JAUNDICE CASES IN EGYPT

Glucose-6-phosphate dehydrogenase (G6PD) deficiency can lead to acute hemolytic anemia, chronic nonspherocytic hemolytic anemia, and neonatal jaundice. Neonatal red cell pyruvate kinase (PK) deficiency may cause clinical patterns, ranging from extremely severe hemolytic anemia to moderate jaundice. The authors aimed at studying the prevalence of G6PD and PK deficiency among Egyptian neonates with pathological indirect hyperbilirubinemia in Cairo. This case-series study included 69 newborns with unconjugated hyperbilirubinemia. All were subjected to clinical history, laboratory investigations, e.g., complete blood counts, reticulocytic counts, direct and indirect serum bilirubin levels, Coombs tests, qualitative assay of G6PD activity by methemoglobin reduction test, and measurement of erythrocytic PK levels. The study detected 10 neonates with G6PD deficiency, which means that the prevalence of G6PD deficiency among Egyptian neonates with hyperbilirubinemia is 14.4% (21.2% of males). G6PD deficiency was significantly higher in males than females (P = .01). The authors detected 2 cases with PK deficiency, making the prevalence of its deficiency 2.8%. These data demonstrate that G6PD deficiency is an important cause for neonatal jaundice in Egyptians. Neonatal screening for its deficiency is recommended. PK deficiency is not a common cause of neonatal jaundice. However, this needs further investigation on a larger scale.     

Glucose-6-phosphate dehydrogenase activity in male premature and term neonates

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) activity is higher in term neonates than in adults. Some studies have suggested that activity may be even higher in preterm infants. OBJECTIVES: To determine if G6PD activity is higher in preterm than term neonates, and whether higher activity would interfere with diagnosis of G6PD deficiency in premature infants. METHODS: G6PD activity was determined in the first 48 hours after delivery in male premature, term, and near term infants. G6PD deficient neonates were separated, and the remaining premature infants compared with healthy, male, G6PD normal, near term and term neonates. RESULTS: Ninety four premature infants (mean (SD) gestational age 31.9 (3.8) weeks (range 23-36)) were studied. In four, G6PD activity was 0.8-1.8 U/g haemoglobin (Hb), which is clearly in the deficient range with no overlap into the normal range. G6PD activity in the remaining premature infants was significantly higher than in 24 near term and term neonates (gestational age > or = 37 weeks) (14.2 (4.6) v 12.0 (3.8) U/g Hb). Further analysis showed that significance was limited to those born between 29 and 32 weeks gestation, in which group G6PD activity was significantly higher than in those born before 29 weeks gestation, at 33-36 weeks gestation, and > or = 37 weeks gestation. CONCLUSIONS: G6PD activity is higher in premature infants born between 29 and 32 weeks gestation than in term neonates. This did not interfere with diagnosis of G6PD deficiency.     

Neonatal Hyperbilirubinemia in infants with G6PD c.563C > T Variant

ABSTRACT: BACKGROUND: There is a strong correlation between glucose-6-phosphate dehydrogenase (G6PD) deficiency and neonatal hyperbilirubinemia with a rare but potential threat of devastating acute bilirubin encephalopathy. G6PD deficiency was observed in 4-14% of hospitalized icteric neonates in Pakistan. G6PD c.563C > T is the most frequently reported variant in this population. The present study was aimed at evaluating the time to onset of hyperbilirubinemia and the postnatal bilirubin trajectory in infants having G6PD c.563C > T. METHODS: This was a case-control study conducted at The Aga Khan University, Pakistan during the year 2008. We studied 216 icteric male neonates who were re-admitted for phototherapy during the study period. No selection was exercised. Medical records showed that 32 were G6PD deficient while 184 were G6PD normal. Each infant was studied for birth weight, gestational age, age at the time of presentation, presence of cephalhematoma, sepsis and neurological signs, peak bilirubin level, age at peak bilirubin level, days of hospitalization, whether phototherapy or exchange blood transfusion was initiated, and the outcome. During hospital stay, each baby was tested for complete blood count, reticulocyte count, ABO and Rh blood type, direct antiglobulin test and quantitative G6PD estimation [by kinetic determination of G6PDH]. G6PDgenotype was analyzed in 32 deficient infants through PCRRFLP analysis and gene sequencing. RESULTS: G6PD variants c.563C > T and c.131 C > G were observed in 21 (65%) and three (9%) of the 32 G6PD deficient infants, respectively. DNA of eight (25%) newborns remained uncharacterized. In contrast to G6PD normal neonates, infants with c.563C > T variant had significantly lower enzyme activity (mean +/- 1SD; 0.3 +/- 0.2 U/gHb vs. 14.0 +/- 4.5 U/gHb, p < 0.001) experienced higher peak levels of total serum bilirubin (mean +/- 1SD; 16.8 +/- 5.4 mg/dl vs. 13.8 +/- 4.6 mg/dl, p = 0.008) which peaked earlier after birth (mean +/- 1SD 2.9 +/- 1.6 vs. 4.3 +/- 2.3 days, p = 0.007). No statistically significant difference was observed in mean weight, age at presentation, hemoglobin, reticulocyte count, TSH level, hospital stay or in the frequency of initiation of phototherapy or blood exchange between the two groups. CONCLUSIONS: We concluded that infants with G6PD c.563C > T variant developed jaundice earlier than infants with normal G6PD enzyme levels. Compared to G6PD normal infants, G6PD c.563C > T carrying infants had significantly low G6PD activity.     

Why does the Iranian National Program of Screening Newborns for G6PD Enzyme Deficiency Miss a Large Number of Affected Infants?

Purpose: G6PD enzyme deficiency is one of the most prevalent genetic disorders worldwide and it has high incidence rate in Northern provinces of Iran. It was observed that national neonatal screening for G6PD enzyme deficiency fails to detect all affected infants. In order to clarify the cause, this study has been done in Thalassemia Research Center, Sari, Iran. Materials and Methods: This was a diagnostic study. The newborns with parents of Mazandarani origin were enrolled. Cord blood from the placental side was collected and used for decolorization test, quantitative enzyme assay (QEA) and DNA study. A heel-prick sample collected on day 3–5 after birth was used for fluorescent spot test (FST). In male cases, QEA was considered as the gold standard. For females, DNA study was considered as the gold standard. Based on QEA test results, neonates with <20% and 20–60% of mean normal enzyme activity were considered as total deficient and partial deficient, respectively. Results: A total of 365 neonates (52.3% females and 47.7% males) were studied. According to FST, 13 male newborns had G6PD deficiency. No deficient female was detected. Decolorization test diagnosed 18 male and one female as G6PD deficient newborns. QEA diagnosed 19 males and 28 females with G6PD enzyme deficiency (26 partial, 2 total deficient cases). DNA analysis detected 14 males as hemizygote and 34 females as heterozygote. Conclusion: FST does not have the required sensitivity for newborn screening and QEA is recommended as the preferred method.     

Enzyme activity of glucose-6-phosphate dehydrogenase-deficient Malaysian neonates during the first 10 days of life

Objective: The objective of this study was to determine the degree of severity of enzyme deficiency in glucose-6-phosphate dehydrogenase (G6PD)-deficient Malaysian neonates as part of an effort to identify risk factors associated with severe hyperbilirubinaemia in G6PD-deficient infants.
Methodology: During this study, enzyme activity was measured in 53/59 (89.8%) hospital-diagnosed G6PD-deficient neonates (34 Malays, 12 Chinese, and seven other ethnic groups) born consecutively in the Kuala Lumpur Maternity Hospital. All neonates, except one, were males.
Results: The mean level of enzyme activity of the 52 males G6PD-deficient neonates (0.47 iu/g Hb, 95% confidence intervals: 0.37, 0.57) was less than 10% of that of normal Malaysian male neonates. The enzyme activity of the only female G6PD-deficient infant, at 1.11 iu/g Hb, was 12.5% of the mean G6PD enzyme activity of normal females.
Conclusion: Our results showed that G6PD deficiency in Malaysian neonates predominantly affects males and is usually severe.     

Glucose-6-phosphate dehydrogenase deficiency in neonates

Objective: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited deficiency that may be the cause of neonatal hyperbilirubinemia, as has been found in several countries and among widely different ethnic groups, especially in Mediterranean region. Our aim was to study the prevalence of G6PD deficiency in relation to neonatal jaundice.Methods : From March 1998 to April 2001 we studied 705 clinically icteric neonates who were admitted to Al-Zahra and Beheshti hospitals, two teaching hospitals in Isfahan, Iran. Laboratory investigations included determination of direct and indirect serum bilirubin concentrations, blood group typing, direct coomb’s test, hemoglobin, blood smear, reticulocyte count and G6PD level.Results: In only 53(7.5%) of cases G6PD deficiency was diagnosed. In all G6PD deficient neonates no evidence of other factors known to cause hyperbilirubinemia were detected. The sex distribution was 13(24.5%)females and 40(75.5%)males in the G6PD deficient group. The mean bilirubin level in G6PD deficient and G6PD normal groups were 22.26 +/-8.36 and 18.14 +/-3.85 mg/dl, respectively (p=0.001). Phototherapy was required in G6PD deficient and other icteric neonates with duration of 3.76 +/-1.93 and 3.13 +/-2.14 days, respectively (p=0.045). Twenty-seven of the 53(50.9%) G6PD deficient infants required exchange transfusion. None of them developed kernicterus.Conclusions: Since the prevalence of severe hyperbilirubinemia among our neonates was relatively high and about half of them required exchange transfusion, early detection of this enzymopathy regardless of sex and close surveillance of the affected newborns may be important in reducing the risk of severe hyperbilirubinemia and exchange transfusion.     

Glucose-6-phosphate dehydrogenase activity, structure, molecular characteristics and role in neonatal hyperbilirubinemia in cord blood in Cukurova region

The most common causes of neonatal indirect hyperbilirubinemia are blood incompatibility and erythrocyte enzyme defects. Glucose-6-phosphate dehydrogenase (G6PD) is a guarantee of erythrocyte stability and capability of existence of red cells. We present here the results of a study on the effect of enzyme kinetics and different mutations on neonatal hyperbilirubinemia in the Cukurova region. Two hundred healthy term male neonates born in Cukurova University Balcall Hospital, Adana Maternity Hospital and Cukurova Maternal and Children's Hospital between 1 November 2004 and 30 November 2007 were consecutively studied. Nanogen DNA microarray was used to determine Gd Union, Gd San, Gd Mediterranean, and Gd San Antonio mutations. Quantitative G6PD enzyme assays were performed. Glucose-6-phosphate dehydrogenase deficiency was detected in six out of 200 male neonates (3%). The other 194 neonates had normal G6PD activity, with a mean of 8.3 +/- 2.1 IU/g hemoglobin (Hb) (5.2-12.7 IU/g Hb). Clinical follow-up, enzyme kinetics and genetic studies were performed in the G6PD-deficient neonates. Differences were observed in clinical outcomes, rates of bilirubin decline and maximum total bilirubin levels in the neonates having the same mutation. These differences might be caused by the effects of kinetic variant on the hyperbilirubinemia without the direct effect of the mutation. In future studies, mutation analyses of further G6PD-deficient cases may address the genotype differences and their clinical effects in G6PD-deficient patients.     

Relationship between Exposure to Icterogenic Agents, Glucose-6-Phosphate Dehydrogenase Deficiency and Neonatal Jaundice in Nigeria

ABSTRACT. In a study of the relationship between exposure to icterogenic agents, G-6-PD deficiency and severe neonatal jaundice (NNJ) (serum bilirubin 3±205 umol/I) in 234 Nigerian term male neonates, 106 infants with severe NNJ and 128 controls, it was found that 62.3 % of the jaundiced infants and 13.3 % of the infants without NNJ were G6PD deficient (p<0.01). The proportion of infants exposed to icterogenic agents in the two groups was very similar (p<0.5). There was a strong association between exposure to icterogenic agents and NNJ in 83 G6PD deficient infants (p<0.01), but there was no association between exposure to icterogenic agents and NNJ in the whole group of 234 infants or in 151 infants with normal G6PD status. It is concluded that there is an association between genetically determined G-6-PD deficiency and exogenous agents in causing severe NNJ in Nigerian infants.     

成都市54025例早产儿葡萄糖-6-磷酸脱氢酶缺乏症筛查结果及分子遗传学特征分析

目的 分析成都市早产儿葡萄糖-6-磷酸脱氢酶(glucose-6-phosphate dehydrogenase,G6PD)缺乏症筛查结果及基因突变分布情况,探讨早产儿人群G6PD筛查流程改进方案.方法 采用干血斑G6PD荧光分析法,对成都市2015年1月1日至2019年12月31日出生的54025例早产儿足跟血样本进...